Cold Spring Harbor Symposia on Quantitative Biology, Volume LXVII.© 2002 Cold Spring Harbor Laboratory Press 0-87969-678-8/02. 189 sels (Dumont et al. 1998; Wigle and Oliver 1999; Wigle et al. 2002). A homeobox transcription factor Prox-1 has been found to have an important role in the formation of the lymph sacs by endothelial cell sprouting from the veins. At the stage when lymphatic development starts, Prox-1 is expressed in a subpopulation of endothelial cells of the anterior cardinal vein. These cells then migrate out and give rise to the lymphatic endothelial cells (Wigle and Oliver 1999). Targeted inactivation of Prox-1 leads to the arrest of the lymphatic endothelial budding process, whereas blood vessel development is not affected (Wigle and Oliver 1999). Another old theory postulates that the lymphatic endothelial cells are derived from mesenchymal precursor cells (Huntington and McClure 1908; Kampmeier 1912). This theory is supported by the recent finding of these precursors, lymphangioblasts, in avian embryonic mesenchyme (Schneider et al. 1999; Papoutsi et al. 2001). Therefore, at least during embryogenesis, both the sprouting lymphangiogenesis and the mesenchymal cell differentiation into lymphatic endothelial cells may contribute to the formation of the lymphatic vessels (Fig. 1).